JPH0650317B2 - Measuring method of viscosity change of blood etc. - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for measuring a change in viscosity of blood or the like.

(Prior Art) In general, it is important to check the viscosity change of blood or the like in order to understand the state of blood or the like. For example, by checking the viscosity change, the blood type can be easily known, It is also widely used in the diagnosis of diseases, for example, by measuring the coagulation time of blood, it is used in the diagnosis of hemophilia, von Willebrand disease, Christmas disease, liver disease, etc. It is also pathologically performed to know the state of the immune reaction by reacting the plasma in the body with the body or body.

Conventionally, as a method for measuring the coagulation time of blood, a method of measuring prothrombin time (PT), a method of measuring activated partial thromboplastin time (APTT),
Typical examples include those based on measurement of thrombin time, fibrinogen test, heparin test and the like.

In addition, examples of a method for testing an immune reaction include a complement supply reaction, a fluorescent reaction, and an enzyme immunoassay method.

In addition, Japanese Patent Application Laid-Open No. 60-15294 previously disclosed by the present applicant.
There is also a method described in Japanese Patent No. 3, which measures the state of thrombus formation by measuring changes in the physical properties of blood in blood vessels.

(Problems to be Solved by the Invention) However, in the conventional method for measuring the change in viscosity of blood or the like as described above, the stimulating substance and the test reagent are commercially available and have a certain stable component. However, it is said that humans mostly judge the coagulation with the naked eye, and the measured values vary, and it is necessary to perform the measurement many times to ensure the reliability. There are difficulties.

There is also a method in which the measurement is carried out by an apparatus, for example, the prothrombin time is measured using a spectrophotometer, but there is a drawback that light scattering due to the incongruity of the liquid surface to be inspected causes a measurement error.

Moreover, the conventional method of measuring by means of devices requires the preparation of devices, instruments, etc. adapted to the respective methods.

And, again, Japanese Patent Application Laid-Open No. 60-15 disclosed by the present applicant.
The measuring method described in Japanese Patent No. 2943 is to investigate thrombus formation due to adhesion of blood cells in an artificial blood vessel, and has not been able to investigate abnormalities in blood and plasma.

The technical problem of the present invention is to solve the above problems, to provide a method for measuring the change in blood viscosity that can be widely used for various measuring methods and can perform measurement without error.

(Means for Solving the Problems) In order to solve the above technical problems, in the present invention, a sensor including a heat absorbing body or a heat generating body is provided in blood or plasma, and the blood or the like is stimulated. This causes a change in viscosity in blood, etc.
Temperature θ _{w of} the heat-absorbing body, surface temperature θ _{s of the} sensor incorporating the heat-generating body, temperatures θ _∞ and θ _w or θ _{s of} blood, etc.
It has to be detected by measuring either the change in the heat transfer coefficient α in kinematic viscosity ν or the sensor surface, such as theta _w - [theta] _∞ or θ _s -θ _∞, blood is the difference between And a method for measuring the change in viscosity of blood or the like.

(Action) Blood coagulation is rapidly performed by fibrin that is finally formed from the activation cascade of coagulation factors, and the viscosity change of blood occurs at that time. And θ _w relating to a sensor composed of an endothermic or exothermic device installed in the blood,
Changes in θ _s , θ _w −θ _∞ , θ _s −θ _∞ , and α are caused.

It is also known that the amount of change in the center temperature and the like and the kinematic viscosity of the fluid have a constant functional relationship. (See Japanese Food Engineering Society, January 1988, Review Article).

Therefore, the kinematic viscosity or an index value related to the kinematic viscosity can be obtained by measuring the amount of change in the temperature of the sensor intermittently or over time, and by using this for the stimulated blood. The change in blood viscosity will be detected. .

Also in the immune reaction system, a large number of minute plastic spheres are added to the blood, and the reaction of the original and the pits is allowed to proceed on the surface of the spheres, and the spheres are eventually aggregated. The immune response will be measured as a change in blood viscosity.

(Example) Hereinafter, the Example of this invention is described.

As an example of the amount of change, the relationship between the amount of change in the temperature difference θ _s −θ _∞ between blood and the surface temperature of the sensor and the kinematic viscosity of blood will be described in detail below.

In FIG. 7, (S) is a sensor, (F) is a container (1
It is the fluid filled in 0).

The steady-state heat transfer coefficient α on the surface of the sensor (S) is given by the following equation, where the calorific value is Q (W) and the surface area of the sensor is A (m ² ).

Therefore, if the calorific value Q and the surface area A of the sensor are known from the equation (1), the heat transfer coefficient can be calculated from the temperature difference θ _s −θ _∞ .

On the other hand, the sensor is set in, for example, distilled water whose physical properties are known, and the temperature difference θ _s between the distilled water and the (heated) sensor is passed through a constant current of various values, for example, a direct current, to the sensor. When −θ _∞ is measured, the Nusselt number Nu, which is a dimensionless amount of heat transfer coefficient, the Prandlt number Pr, which is a dimensionless amount of kinematic viscosity, and the Grashof (dimensional amount of temperature difference). Grashof) The relational expression with the number Gr, that is, an equation for generally expressing the free convection heat transfer phenomenon around the sensor, for example, Nu = C ₀ Gr ^C1 Pr ^C2 (2) is obtained (wherein C ₀ , C ₁ and C ₂ are constants).

Nu, Gr and Pr are represented by the following relational expressions.

Nu = αL / λ (3) Gr = L ³ gβ (θ _s −θ _∞ ) / ν ² (4) Pr = ν / a (5) [wherein L is a representative length (m), λ is the thermal conductivity (w / m
k) and g are gravitational acceleration (m / s ² ), β is volume expansion coefficient (1 / K), ν is kinematic viscosity (m ² / s), and a is temperature transfer coefficient (w / m ² · K). Are shown respectively. Therefore, the kinematic viscosity ν of the substance to be measured is expressed by the above equation (2) to
It is expressed by the following formula from (5).

_{^{ν 2C1-C2 = C og C1}} AL 3C1-1 Q -1 λβ C1 a -C2 (θ s -θ ∞)
^{C1 + 1} (6) Here, for example, when a platinum wire that is electrically heated at a current i is used as a sensor Q = Ri ² (7) [where R is the electricity of the platinum wire used as the sensor] The resistance (Ω) and i represent the current value (A) applied to the sensor. In the above equation (6), g, A, and L are constants, and the changes in λ, β, and a are sufficiently smaller than the change width of ν, so that the kinematic viscosity ν is the calorific value Q. And θ _s
It is expressed by the following equation (8) as a function of only −θ _∞ .

ν ^2C1-C2 = C ₃ Q ^-1 (θ _s -θ _∞ ) ^{C1 + 1} (8) [wherein C ₃ represents a constant. ] Then, blood is used as the fluid (F) and an electric current is applied to the sensor (S) so that the calorific value Q is constant, and the change amount θ _s −θ _∞ of the temperature difference between the blood and the sensor is measured. Thus, the kinematic viscosity ν is obtained, and the viscosity change is detected.

The results of experiments conducted by the present inventors are shown below.

In the experiment, various reagents were injected into a normal human plasma (VNC) sample, and the subsequent coagulation change process was continuously measured using a sensor.

In FIG. 7, (M) is a measuring device system that controls the sensor (S), (1) is a current source, (2) is a voltage measuring device, and (3) is a control device. -IB
(General purpose interface bus).

Then, the temperature of the sensor (S) as described above can be easily known by the usual method by calculating the resistance value from the applied voltage value and current value, and the blood temperature is also measured by the side temperature low antibody etc. It is what is done.

<Experimental Example 1> A coagulation factor and a stimulant consisting of tissue tramoplastin and calcium chloride were co-injected into normal whole blood, normal plasma, abnormal whole blood, and abnormal plasma, respectively, and the protobin time (P
T) was measured.

Each test solution was prepared in Spitz equipped with a sensor consisting of a platinum wire with a resistance of about 50Ω at 0 ° C,
The sensor was heated with A or a current of about 60 mA.

Table 1 shows each protobin time (PT), and FIG. 1 shows the amount of change in temperature difference θ _s −θ _∞ when the abnormal plasma among them was used as the test liquid and the sensor heating current was 40 mA. 2 shows the relationship between the time and the elapsed time, and FIG. 2 shows the case where normal plasma is used as the test liquid and the sensor heating current is about 40 mA.

In each figure, the horizontal axis represents the elapsed time with the time of preparation of the test liquid as 0, the upper figure is a graph showing the change rate of the temperature difference with respect to the elapsed time, and the lower figure shows the temperature with respect to the elapsed time. It is a graph showing the change of the difference.

<Experimental example 2> A coagulation factor stimulating substance such as kaolin, phospholipid, celite, silicic acid, and ellagic acid was co-injected into each of normal whole blood, normal plasma, abnormal whole blood, and abnormal plasma, and activated partial thromboplastin time. (APTT) was measured.

Create each test solution in Spitz equipped with a thin metal wire,
The sensor heating current was about 40 mA.

Table 2 shows each activated partial thromboplastin time (APTT). FIG. 3 shows abnormal plasma among them as the test liquid, and the sensor heating current was about 40 mA.
Fig. 4 shows the relationship between the amount of change in temperature difference θ _s -θ _∞ and the elapsed time, when Fig. 4 shows that normal plasma was used as the test liquid and the sensor heating current was about 40 mA. It is a thing.

<Experimental Example 3> The thrombin time was measured stepwise in a plasma sample having a fibrin deposition concentration of 1 to 20%.

The sensor heating current was about 60 mA.

Table 3 shows each thrombin time, and FIG. 5 shows the relationship between the change amount of temperature difference θ _s −θ _∞ and the elapsed time when the concentration of fibrin precipitation is 1%. Yes, FIG. 6 is when the fibrin precipitation concentration is 20%.

(Effects of the Invention) As described above, according to the method of the present invention, the viscosity change is measured by stimulating the blood to coagulate the blood to measure the viscosity change. Extremely easy and accurate.

Therefore, the blood type can be easily known.

Further, for example, the diagnosis of a seriously ill person whose blood coagulation time is long can be performed without being affected by the low viscosity,
In addition, since small changes in coagulation can be easily detected, the error caused in diagnostic measurement is extremely small.

Therefore, there is no need to measure many times as in the past,
This will reduce the time and labor required for measurement.

In addition, it is economical because there is no need to prepare equipment and instruments for various tests.

[Brief description of drawings]

1 to 6 are graphs showing the results measured by the method of the present invention, and FIG. 7 is an explanatory view of the measurement state. (F) …… Fluid (S) …… Sensor (M) …… Measuring device system (1) …… Current source (2) …… Voltage measuring device (3) …… Control device

Claims (4)

[Claims] 1. A sensor comprising a heat absorbing body or a heat generating body is installed in blood or plasma, and the blood or the like is stimulated to cause a viscosity change in the blood or the like. Body temperature θ _w , surface temperature θ _{s of the} sensor with built-in heat absorbing / heating element, temperature θ _{∞ of} blood, etc.
And θ _w or θ _s , which is the difference between θ _w −θ _∞ or θ _s −
A method for measuring a viscosity change of blood or the like, characterized in that it is detected by measuring either θ _∞ , a kinematic viscosity ν of blood or the like or a heat transfer coefficient α of the sensor surface. 2. The stimulation of blood or the like is performed by adding a factor that activates blood coagulation (1).
The method for measuring the change in viscosity of blood, etc. 3. The method for measuring the viscosity change of blood or the like according to claim 1, wherein the stimulation of the blood or the like is performed by means of adding a raw material or a hollow body. 4. The method for measuring the change in viscosity of blood or the like according to claim 1, wherein the stimulation of blood or the like is performed by physical means.